Continuous renal replacement therapy allows higher colistin dosing without increasing toxicity

Polymyxins are "old'' antimicrobials which were abandoned for almost 30 years because of significant renal and neurological toxicity. However, the alarming rise of multi-resistant Gramnegative bacterial infections worldwide has revived interest in these "forgotten'' agents. Colistin (polymyxin E) is one of the main antibiotics of this class. It is most often administered as the pro-drug colistimethate sodium. Doses for treatment of systemic infections in adults range between 3 and 9 million IU per day. Colistin is increasingly used for treatment of pneumonia and bacteremia in critically ill patients. During their ICU stay, many of these subjects will need continuous renal replacement therapy (CRRT) because of acute kidney injury or an unstable hemodynamic condition. Based on recent pharmacological data and own experience, we postulate that patients undergoing CRRT may receive substantially higher doses of colistin (i.e., a high loading dose, followed by a maintenance dose up to 4.5 million IU tid). Treatment can be continued for a prolonged time period without increasing toxicity. CRRT counteracts colistin accumulation because the drug is continuously filtered and also significantly adsorbed in the bulk of the dialysis membrane. Implementing such "CRRT rescue'' therapy does require the strict use of highly adsorptive dialysis membranes in association with citrate anticoagulation to increase membrane performance.